Many Worried About Lowering FDA Standards: LA Times
By lowering FDA regulatory standards as president Donald Trump promised pharmaceutical makers last week at the White House, many FDA watchers fear patients could be exposed to ineffective therapies until data gathered after marketing approval demonstrate effectiveness. Trump reportedly is considering several commissioner candidates that argue for quicker market access for therapies by limiting their effectiveness data to gain approval.
To illustrate the concern, the Los Angeles Times outlined 2/6 how Genentech and OSI Pharmaceuticals gained an expanded approval on limited data in 2010 for Tarceva (erlotinib) and its use in non-small cell lung cancer patients, notwithstanding a 12-1 negative advisory committee recommendation the year before. The indication was eventually modified six years later for a small subset of patients after a trial that FDA ordered showed that Tarceva was only effective in patients with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitutions.
Study data contradicting the drug’s effectiveness in a broader patient population in 2016 led to a revised label, but much damage had already been done, investigative reporter Melody Petersen wrote. “The FDA’s decision resulted in more harm than the hundreds of millions of dollars wasted on a drug that was ineffective for 90% or more of patients,” her report says. ”Over the years, thousands of patients were prescribed a drug that had no chance of helping them but could frequently cause terrible rashes covering their faces and bodies, according to prescription data and adverse event reports. Some patients with the most aggressively growing cancers died before trying other treatments that may have lengthened their lives.”
To make matters worse, the government alleged the companies were violating advertising and promotion rules when marketing Tarceva. The Justice Department said in 2016 that Genentech and OSI agreed to pay $67 million to resolve a whistleblower’s False Claims Act allegations about misleading statements on the drug’s effectiveness. A department statement said the allegations claimed that between 1/2006 and 12/2011 the two companies made misleading representations to doctors and other healthcare providers about Tarceva’s effectiveness to treat certain patients with non-small cell lung cancer when there was little evidence to show that the drug was effective to treat those patients unless they also had never smoked or had a mutation in their epidermal growth factor receptor.
Vinay Prasad, a hematologist-oncologist at Oregon Health and Science University who has studied the FDA’s accelerated approval of cancer drugs, told the newspaper that FDA’s lax approval standards, combined with the six-figure prices companies can charge for unproven or marginal medicines, have encouraged the industry to take marketing shortcuts rather than spend research dollars to find true breakthroughs. He pointed to a study that found the average gain in survival for the 71 cancer drugs approved from 2002 to 2014 was just 2.1 months.“That’s not good enough for the people I see in my clinic,” he said. “As you lower the regulatory standards you open the flood gates to more of these ineffective drugs.”
In a separate study, Prasad and his colleague found that of 36 cancer drugs approved by FDA between 2008 and 2012, only five had been shown to actually extend survival by 2015. “Some ineffective drugs have eventually been taken off the market, but it can take years,” according to Petersen’s article. “A drug called Mylotarg was pulled from pharmacy shelves in 2010 — 10 years after the FDA approved it for acute myeloid leukemia, a bone marrow cancer.”
The FDA told the newspaper that it had limited the drug’s approval in 2016 to the small number of patients who had the mutation soon after Genentech released the results of the study last year showing it did not work for other patients. The agency had requested that study six years earlier. FDA officials attributed the delay in limiting Tarceva’s approval to the many years it can take to perform a meaningful scientific study. “This process of gaining new knowledge about disease and drug efficacy — which can significantly modify or even contradict results on which previous drug approval decisions were made — is the essence of scientific advancement,” it said.